Abdominopelvic mass in postmenopausal female: a diagnostic dilemma

Abdominopelvic masses have varied presentations and pose a diagnostic challenge especially in postmenopausal women where a detailed evaluation is needed to rule out malignancy. Here we report a case of postmenopausal woman with diagnostic discrepancies in clinical findings, radiological investigations and histopathological observation

In silico identification and characterization of the SNPs in the human ASTL gene and their probable role in female infertility

Ovastacin (ASTL), a zinc metalloprotease, is released from a fertilized egg during exocytosis of cortical granules which occurs minutes after the sperm and egg fuse. ASTL cleaves ZP2, one of the four primary glycoproteins of human zona pellucida, and this cleavage prevents polyspermy, causes zona pellucida hardening, and also protects the pre-implantation embryo. Any perturbation in the activity of ASTL can thus disturb this process and may lead to infertility without changing the gross morphology of the oocyte. A small amount of ASTL is also released by unfertilized oocytes but its catalytic activity is absent as it is bound by its inhibitor, Fetuin-B (FETUB). Pre-mature release of ASTL when FETUB is absent also causes infertility. To identify and understand the structural and functional effects of deleterious SNPs of ASTL on its interaction with ZP2 and FETUB and hence on fertility, a total of 4,748 SNPs from the dbSNP database were evaluated using a variety of in silico tools. All of the 40 shortlisted nsSNPs were present in the catalytic domain of the protein. Comparison of the wild type with mutants using MutPred2 suggests an alteration in the catalytic activity/zinc binding site in many SNPs. Docking studies show the involvement of hydrophobic interactions and H bonding between ASTL and ZP2 and also between ASTL and FETUB. Four positions in ASTL involved in the hydrophobic interactions (P105 and D200 between ASTL and ZP2; D198 and L278 between ASTL and FETUB) and 5 in H bonding (E75 and R159 between ASTL and ZP2; and K93, R159, and C281 between ASTL and FETUB) have SNP’s associated with them validating their importance. Interestingly, a cluster of multiple SNPs was found in the motif 198DRD200, which is also a well-conserved region among several species. Statistical Coupling Analysis (SCA) suggested that the deleterious SNPs were present in the functionally important amino acid positions of ASTL and are evolutionarily coupled. Thus, these results attempt to identify the regions in ASTL, mutations in which can affect its binding with ZP2 or FETUB and cause female infertility

Evaluation of Gamma glutamyl-transferase (GGT) levels in COVID-19: A retrospective analysis in tertiary care centre

Many recent studies have reported that patients infected with novel coronavirus 2019 or SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) might have a liver injury. However, few studies have focussed on the levels of Gamma glutamyl-transferase (GGT) alone and the variations associated with it. We retrospectively analysed the GGT levels of 476 admitted patients with confirmed COVID-19 in a tertiary care centre, PGIMER (Post Graduate Institute of Medical Education and Research), Chandigarh. Out of the total 476 COVID-19 patients studied, 35% had elevated GGT levels. ICU care was required for 51.19% (P <0.0001) of these patients and their hospital stay was of longer duration as compared to the patients with normal GGT levels. The incidence of GGT elevation was found to be more pronounced in males and elderly patients. The male population displayed higher GGT levels with 52% having raised levels compared to females where only 21.6% had elevated GGT levels. Although the number of COVID-19 cases was majorly from young age groups, the elevation in GGT levels has been reported more in elderly patients. GGT levels can therefore serve as a predictor for the extent of liver injury and severity in COVID-19 patients

Evaluation of Gamma glutamyl-transferase (GGT) levels in COVID-19: A retrospective analysis in tertiary care centre

681-686Many recent studies have reported that patients infected with novel coronavirus 2019 or SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) might have a liver injury. However, few studies have focussed on the levels of Gamma glutamyl-transferase (GGT) alone and the variations associated with it. We retrospectively analysed the GGT levels of 476 admitted patients with confirmed COVID-19 in a tertiary care centre, PGIMER (Post Graduate Institute of Medical Education and Research), Chandigarh. Out of the total 476 COVID-19 patients studied, 35% had elevated GGT levels. ICU care was required for 51.19% (P <0.0001) of these patients and their hospital stay was of longer duration as compared to the patients with normal GGT levels. The incidence of GGT elevation was found to be more pronounced in males and elderly patients. The male population displayed higher GGT levels with 52% having raised levels compared to females where only 21.6% had elevated GGT levels. Although the number of COVID-19 cases was majorly from young age groups, the elevation in GGT levels has been reported more in elderly patients. GGT levels can therefore serve as a predictor for the extent of liver injury and severity in COVID-19 patients

Prevalence of stunting among under-five children in refugee and internally displaced communities: a systematic review and meta-analysis

BackgroundA pooled estimate of stunting prevalence in refugee and internally displaced under-five children can help quantify the problem and focus on the nutritional needs of these marginalized groups. We aimed to assess the pooled prevalence of stunting in refugees and internally displaced under-five children from different parts of the globe.MethodsIn this systematic review and meta-analysis, seven databases (Cochrane, EBSCOHost, EMBASE, ProQuest, PubMed, Scopus, and Web of Science) along with “preprint servers” were searched systematically from the earliest available date to 14 February 2023. Refugee and internally displaced (IDP) under-five children were included, and study quality was assessed using “National Heart, Lung, and Blood Institute (NHLBI)” tools.ResultsA total of 776 abstracts (PubMed = 208, Scopus = 192, Cochrane = 1, Web of Science = 27, Embase = 8, EBSCOHost = 123, ProQuest = 5, Google Scholar = 209, and Preprints = 3) were retrieved, duplicates removed, and screened, among which 30 studies were found eligible for qualitative and quantitative synthesis. The pooled prevalence of stunting was 26% [95% confidence interval (CI): 21–31]. Heterogeneity was high (I2 = 99%, p < 0.01). A subgroup analysis of the type of study subjects revealed a pooled stunting prevalence of 37% (95% CI: 23–53) in internally displaced populations and 22% (95% CI: 18–28) among refugee children. Based on geographical distribution, the stunting was 32% (95% CI: 24–40) in the African region, 34% (95% CI: 24–46) in the South-East Asian region, and 14% (95% CI: 11–19) in Eastern Mediterranean region.ConclusionThe stunting rate is more in the internally displaced population than the refugee population and more in the South-East Asian and African regions. Our recommendation is to conduct further research to evaluate the determinants of undernutrition among under-five children of refugees and internally displaced populations from different regions so that international organizations and responsible stakeholders of that region can take effective remedial actions.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=387156, PROSPERO [CRD42023387156]

Drug Discovery for Duchenne Muscular Dystrophy via Utrophin Promoter Activation Screening

Background: Duchenne muscular dystrophy (DMD) is a devastating muscle wasting disease caused by mutations in dystrophin, a muscle cytoskeletal protein. Utrophin is a homologue of dystrophin that can functionally compensate for its absence when expressed at increased levels in the myofibre, as shown by studies in dystrophin-deficient mice. Utrophin upregulation is therefore a promising therapeutic approach for DMD. The use of a small, drug-like molecule to achieve utrophin upregulation offers obvious advantages in terms of delivery and bioavailability. Furthermore, much of the time and expense involved in the development of a new drug can be eliminated by screening molecules that are already approved for clinical use. Methodology/Principal Findings: We developed and validated a cell-based, high-throughput screening assay for utrophin promoter activation, and used it to screen the Prestwick Chemical Library of marketed drugs and natural compounds. Initial screening produced 20 hit molecules, 14 of which exhibited dose-dependent activation of the utrophin promoter and were confirmed as hits. Independent validation demonstrated that one of these compounds, nabumetone, is able to upregulate endogenous utrophin mRNA and protein, in C2C12 muscle cells. Conclusions/Significance: We have developed a cell-based, high-throughput screening utrophin promoter assay. Using this assay, we identified and validated a utrophin promoter-activating drug, nabumetone, for which pharmacokinetics an